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Gene Review

PDR1  -  Pdr1p

Saccharomyces cerevisiae S288c

Synonyms: AMY1, ANT1, BOR2, CYH3, NRA2, ...
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Disease relevance of PDR1

  • These data underscore the role of the pleiotropic drug resistance network in regulating camptothecin toxicity and are consistent with a model of decreased intracellular concentrations of camptothecin resulting from the increased expression of the SNQ2 transporter [1].
  • Here we show that disruption of C. glabrata PDR1 conferred equivalent fluconazole hypersensitivity (MIC = 2 microg ml(-1)) to both F15 and 66032 and eliminated both constitutive and fluconazole-induced CDR1-PDH1 expression [2].
  • Mutations in the human ANT1 gene, coding for the ADP/ATP carrier, are responsible for the autosomal dominant and recessive forms of progressive external ophthalmoplegia, mitochondrial disorders characterized by the presence of multiple deletions of mitochondrial DNA in affected tissues [3].

High impact information on PDR1

  • Targeting of Ant1p to peroxisomes was dependent on Pex3p and Pex19p, two peroxins specifically required for peroxisomal membrane protein insertion [4].
  • Ant1p was found to be an integral protein of the peroxisomal membrane and expression of ANT1 was oleic acid inducible [4].
  • This and the observed repression of apoptosis by the ANT-1-interacting protein cyclophilin D suggest that the suicidal effect of ANT-1 is mediated by specific protein-protein interactions within the permeability transition pore [5].
  • We discovered a nuclear import pathway mediated by the product of the previously identified Saccharomyces cerevisiae gene PDR6 (pleiotropic drug resistance) [6].
  • Complementation cloning and linkage analysis led to the identification of the dominant mutation TPE1-1 as a new allele of PDR1 and the semidominant mutation tpe2-1 as a new allele of PDR3 [7].

Chemical compound and disease context of PDR1


Biological context of PDR1


Anatomical context of PDR1

  • Concomitantly, the level of PDR5 mRNA, of Pdr5p protein, and of its associated nucleoside triphosphatase activity, was strongly increased in the plasma membranes of the PDR1 mutants [12].
  • Multiple signals from dysfunctional mitochondria activate the pleiotropic drug resistance pathway in Saccharomyces cerevisiae [13].
  • The transcription regulators, PDR1 and PDR3, have been shown to activate the transcription of numerous genes involved in a wide range of functions, including resistance to physical and chemical stress, membrane transport, and organelle function in Saccharomyces cerevisiae [7].
  • These data suggest that Pdr1p and Pdr3p may act to modulate the lipid composition of membranes in S. cerevisiae through activation of sphingolipid biosynthesis along with other target genes [14].
  • No Delta pH was present in ant1 Delta cells, indicating that the peroxisomal pH is regulated in an ATP-dependent way and suggesting that Ant1p activity is directly involved in maintenance of the peroxisomal pH [15].

Associations of PDR1 with chemical compounds


Physical interactions of PDR1

  • Transcriptional activation by a GAL4p DNA binding domain fusion of PDR1p was enhanced in ngg1 and ada2 disruption strains [20].
  • The putative consensus Yrr1p binding site deduced from these experiments, (T/A)CCG(C/T)(G/T)(G/T)(A/T)(A/T), is strikingly similar to the PDR element binding site sequence recognized by Pdr1p and Pdr3p [21].
  • In addition, in vitro band shift assays demonstrate that a GST-Pdr1 fusion protein can bind to the PDREs of PDR10 and PDR15 [22].
  • We show here that the RPN4 gene promoter contains regulatory sequences that bind Pdr1p and Pdr3p, two homologous zinc finger-containing transcription factors, which mediate multiple drug resistance through the expression of membrane transporter proteins [23].
  • In this study, we have found that there are three sites in the PDR5 5'-noncoding region that are closely related to one another and are bound by both Pdr1p and Pdr3p [24].

Regulatory relationships of PDR1


Other interactions of PDR1

  • Expression of these genes is under the control of two homologous zinc finger-containing transcription regulators, Pdr1p and Pdr3p [27].
  • The PDR1 T879M mutant increased PDR5 transcription compared with wild-type PDR1 strains [1].
  • Amino acids 274-307 of NGG1p were required for interaction with PDR1p [20].
  • Similar to its action on GAL4p, the ADA complex acts to inhibit the activation domain of PDR1p [20].
  • The ATP-binding cassette multidrug transporter Snq2 of Saccharomyces cerevisiae: a novel target for the transcription factors Pdr1 and Pdr3 [17].

Analytical, diagnostic and therapeutic context of PDR1

  • Functional dissection of Pdr1p, a regulator of multidrug resistance in Saccharomyces cerevisiae [25].
  • Genetic and Western blotting experiments indicated that Pdr13p exerts its effect on Pdr1p at a posttranslational step [9].
  • We found that the regulation of these four genes depends on Pdr1p, since promoter activities studied by lacZ fusion analysis and mRNA levels studied by Northern blotting analysis changed upon deletion or hyperactivation by the pdr1-3 mutant of this transcription factor [28].
  • To identify novel targets of Pdr1p, we compared transcriptomes among the yeast cells bearing wild, disrupted and gain-of-function alleles of PDR1 using a high-throughput fluorescent differential display PCR [29].
  • Active efflux by multidrug transporters as one of the strategies to evade chemotherapy and novel practical implications of yeast pleiotropic drug resistance [30].


  1. Camptothecin sensitivity is mediated by the pleiotropic drug resistance network in yeast. Reid, R.J., Kauh, E.A., Bjornsti, M.A. J. Biol. Chem. (1997) [Pubmed]
  2. Pdr1 regulates multidrug resistance in Candida glabrata: gene disruption and genome-wide expression studies. Vermitsky, J.P., Earhart, K.D., Smith, W.L., Homayouni, R., Edlind, T.D., Rogers, P.D. Mol. Microbiol. (2006) [Pubmed]
  3. Mutation D104G in ANT1 gene: complementation study in Saccharomyces cerevisiae as a model system. Lodi, T., Bove, C., Fontanesi, F., Viola, A.M., Ferrero, I. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  4. Identification and functional reconstitution of the yeast peroxisomal adenine nucleotide transporter. Palmieri, L., Rottensteiner, H., Girzalsky, W., Scarcia, P., Palmieri, F., Erdmann, R. EMBO J. (2001) [Pubmed]
  5. Adenine nucleotide translocase-1, a component of the permeability transition pore, can dominantly induce apoptosis. Bauer, M.K., Schubert, A., Rocks, O., Grimm, S. J. Cell Biol. (1999) [Pubmed]
  6. The karyopherin Kap122p/Pdr6p imports both subunits of the transcription factor IIA into the nucleus. Titov, A.A., Blobel, G. J. Cell Biol. (1999) [Pubmed]
  7. Plasma membrane translocation of fluorescent-labeled phosphatidylethanolamine is controlled by transcription regulators, PDR1 and PDR3. Kean, L.S., Grant, A.M., Angeletti, C., Mahé, Y., Kuchler, K., Fuller, R.S., Nichols, J.W. J. Cell Biol. (1997) [Pubmed]
  8. Two nuclear proteins, Cin5 and Ydr259c, confer resistance to cisplatin in Saccharomyces cerevisiae. Furuchi, T., Ishikawa, H., Miura, N., Ishizuka, M., Kajiya, K., Kuge, S., Naganuma, A. Mol. Pharmacol. (2001) [Pubmed]
  9. Regulation of transcription factor Pdr1p function by an Hsp70 protein in Saccharomyces cerevisiae. Hallstrom, T.C., Katzmann, D.J., Torres, R.J., Sharp, W.J., Moye-Rowley, W.S. Mol. Cell. Biol. (1998) [Pubmed]
  10. Diazaborine resistance in the yeast Saccharomyces cerevisiae reveals a link between YAP1 and the pleiotropic drug resistance genes PDR1 and PDR3. Wendler, F., Bergler, H., Prutej, K., Jungwirth, H., Zisser, G., Kuchler, K., Högenauer, G. J. Biol. Chem. (1997) [Pubmed]
  11. Mutations in the yeast PDR3, PDR4, PDR7 and PDR9 pleiotropic (multiple) drug resistance loci affect the transcript level of an ATP binding cassette transporter encoding gene, PDR5. Dexter, D., Moye-Rowley, W.S., Wu, A.L., Golin, J. Genetics (1994) [Pubmed]
  12. Molecular and phenotypic characterization of yeast PDR1 mutants that show hyperactive transcription of various ABC multidrug transporter genes. Carvajal, E., van den Hazel, H.B., Cybularz-Kolaczkowska, A., Balzi, E., Goffeau, A. Mol. Gen. Genet. (1997) [Pubmed]
  13. Multiple signals from dysfunctional mitochondria activate the pleiotropic drug resistance pathway in Saccharomyces cerevisiae. Hallstrom, T.C., Moye-Rowley, W.S. J. Biol. Chem. (2000) [Pubmed]
  14. Coordinate control of sphingolipid biosynthesis and multidrug resistance in Saccharomyces cerevisiae. Hallstrom, T.C., Lambert, L., Schorling, S., Balzi, E., Goffeau, A., Moye-Rowley, W.S. J. Biol. Chem. (2001) [Pubmed]
  15. The peroxisomal lumen in Saccharomyces cerevisiae is alkaline. van Roermund, C.W., de Jong, M., IJlst, L., van Marle, J., Dansen, T.B., Wanders, R.J., Waterham, H.R. J. Cell. Sci. (2004) [Pubmed]
  16. The ATP binding cassette transporters Pdr5 and Snq2 of Saccharomyces cerevisiae can mediate transport of steroids in vivo. Mahé, Y., Lemoine, Y., Kuchler, K. J. Biol. Chem. (1996) [Pubmed]
  17. The ATP-binding cassette multidrug transporter Snq2 of Saccharomyces cerevisiae: a novel target for the transcription factors Pdr1 and Pdr3. Mahé, Y., Parle-McDermott, A., Nourani, A., Delahodde, A., Lamprecht, A., Kuchler, K. Mol. Microbiol. (1996) [Pubmed]
  18. The transporters Pdr5p and Snq2p mediate diazaborine resistance and are under the control of the gain-of-function allele PDR1-12. Wehrschütz-Sigl, E., Jungwirth, H., Bergler, H., Högenauer, G. Eur. J. Biochem. (2004) [Pubmed]
  19. The multidrug resistance gene PDR1 from Saccharomyces cerevisiae. Balzi, E., Chen, W., Ulaszewski, S., Capieaux, E., Goffeau, A. J. Biol. Chem. (1987) [Pubmed]
  20. Transcriptional activation by yeast PDR1p is inhibited by its association with NGG1p/ADA3p. Martens, J.A., Genereaux, J., Saleh, A., Brandl, C.J. J. Biol. Chem. (1996) [Pubmed]
  21. New insights into the pleiotropic drug resistance network from genome-wide characterization of the YRR1 transcription factor regulation system. Le Crom, S., Devaux, F., Marc, P., Zhang, X., Moye-Rowley, W.S., Jacq, C. Mol. Cell. Biol. (2002) [Pubmed]
  22. The yeast ATP binding cassette (ABC) protein genes PDR10 and PDR15 are novel targets for the Pdr1 and Pdr3 transcriptional regulators. Wolfger, H., Mahé, Y., Parle-McDermott, A., Delahodde, A., Kuchler, K. FEBS Lett. (1997) [Pubmed]
  23. Control of 26S proteasome expression by transcription factors regulating multidrug resistance in Saccharomyces cerevisiae. Owsianik, G., Balzi l, L., Ghislain, M. Mol. Microbiol. (2002) [Pubmed]
  24. Multiple Pdr1p/Pdr3p binding sites are essential for normal expression of the ATP binding cassette transporter protein-encoding gene PDR5. Katzmann, D.J., Hallstrom, T.C., Mahé, Y., Moye-Rowley, W.S. J. Biol. Chem. (1996) [Pubmed]
  25. Functional dissection of Pdr1p, a regulator of multidrug resistance in Saccharomyces cerevisiae. Kolaczkowska, A., Kolaczkowski, M., Delahodde, A., Goffeau, A. Mol. Genet. Genomics (2002) [Pubmed]
  26. Cross talk between sphingolipids and glycerophospholipids in the establishment of plasma membrane asymmetry. Kihara, A., Igarashi, Y. Mol. Biol. Cell (2004) [Pubmed]
  27. Multiple-drug-resistance phenomenon in the yeast Saccharomyces cerevisiae: involvement of two hexose transporters. Nourani, A., Wesolowski-Louvel, M., Delaveau, T., Jacq, C., Delahodde, A. Mol. Cell. Biol. (1997) [Pubmed]
  28. Novel target genes of the yeast regulator Pdr1p: a contribution of the TPO1 gene in resistance to quinidine and other drugs. do Valle Matta, M.A., Jonniaux, J.L., Balzi, E., Goffeau, A., van den Hazel, B. Gene (2001) [Pubmed]
  29. Differential display analysis of mutants for the transcription factor Pdr1p regulating multidrug resistance in the budding yeast. Miura, F., Yada, T., Nakai, K., Sakaki, Y., Ito, T. FEBS Lett. (2001) [Pubmed]
  30. Active efflux by multidrug transporters as one of the strategies to evade chemotherapy and novel practical implications of yeast pleiotropic drug resistance. Kolaczkowski, M., Goffeau, A. Pharmacol. Ther. (1997) [Pubmed]
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